TY - JOUR
T1 - Atomistic details of charge/space competition in the Ca2+selectivity of ryanodine receptors
AU - Liu, Chunhong
AU - Zhang, Aihua
AU - Yan, Nieng
AU - Song, Chen
N1 - Funding Information:
We thank Prof. Wayne S.R. Chen for very helpful discussions. This research was supported by the National Natural Science Foundation of China (21873006 and 32071251) and the National Key Research & Development Program of the Ministry of Science and Technology of China (2016YFA0500400). Part of the molecular dynamics simulation was performed on the Computing Platform of the Center for Life Sciences at Peking University.
Publisher Copyright:
© 2021 The Authors. Published by American Chemical Society.
PY - 2021/5/6
Y1 - 2021/5/6
N2 - Ryanodine receptors (RyRs) are ion channels responsible for the fast release of Ca2+ from the sarco/endoplasmic reticulum to the cytosol and show a selectivity of Ca2+ over monovalent cations. By utilizing a recently developed multisite Ca2+ model in molecular dynamic simulations, we show that multiple cations accumulate in the upper selectivity filter of RyRs, and the small size and high valence of Ca2+ make it preferable to K+ in competition for space in this confined region of negative electrostatic potential. The presence of Ca2+ in the upper selectivity filter significantly increases the energy barrier of K+ permeation, while the presence of K+ has little impact on the Ca2+ permeation. Our results provide the atomistic details of the charge/space competition mechanism for the ion selectivity of RyRs, which ensures the robustness of their Ca2+ release function. The mechanism could be utilized in protein- and nanoengineering for valence selectivity of ion species.
AB - Ryanodine receptors (RyRs) are ion channels responsible for the fast release of Ca2+ from the sarco/endoplasmic reticulum to the cytosol and show a selectivity of Ca2+ over monovalent cations. By utilizing a recently developed multisite Ca2+ model in molecular dynamic simulations, we show that multiple cations accumulate in the upper selectivity filter of RyRs, and the small size and high valence of Ca2+ make it preferable to K+ in competition for space in this confined region of negative electrostatic potential. The presence of Ca2+ in the upper selectivity filter significantly increases the energy barrier of K+ permeation, while the presence of K+ has little impact on the Ca2+ permeation. Our results provide the atomistic details of the charge/space competition mechanism for the ion selectivity of RyRs, which ensures the robustness of their Ca2+ release function. The mechanism could be utilized in protein- and nanoengineering for valence selectivity of ion species.
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U2 - 10.1021/acs.jpclett.1c00681
DO - 10.1021/acs.jpclett.1c00681
M3 - Article
C2 - 33909426
AN - SCOPUS:85106143793
SN - 1948-7185
VL - 12
SP - 4286
EP - 4291
JO - Journal of Physical Chemistry Letters
JF - Journal of Physical Chemistry Letters
IS - 17
ER -